Anterior vaginal wall prolapse (AVP), clinically known as cystocele, is the most common form of pelvic organ prolapse. The NICHD Female Pelvic Floor Disorders workgroup and NIDDK'S Bladder Progress Review Group have identified a critical need for pathophysiology research in these conditions. Competing hypotheses have been proposed to explain how anterior vaginal wall connective tissue support (CIS) failure results in AVP; midline stretching of the vaginal wall vs. peripheral detachment in the paravaginal and apical areas of support. However, these theories do not incorporate observations from our previous funding cycle that pubococcygeal muscle (PCM) damage is 4 times more common in women with prolapse. This study proposes to test mechanistic hypotheses that the occurrence and magnitude of AVP is not explained by a single mechanism but involves the interaction of different connective tissue failures sites and also PCM impairment. We will use MRI techniques and novel 3-D computer modeling to individually measure and compare the status of each site of support in 150 women with AVP and 150 controls. In Aim 1 we will: a) measure origin to insertion distances for paravaginal and apical supports and longitudinal and transverse diameters of the vaginal wall at maximum Valsalva to determine the contribution of CTS failures at these sites to the presence of AVP, b) determine the sites where each individual with AVP has measures outside the normal range found in controls and c) use linear regression models to determine how the number of CTS site defects and severity of CTS failure at each site affects AVP size. In Aim 2 we will: a) determine how muscle impairment interacts with CTS failure in explaining the occurrence and size of AVP by measuring muscle structure and function in both groups, b) examine the role that PCM impairment plays in determining AVP severity beyond the contribution of the CTS and c) determine whether patterns of CTS failure (e.g. single failure, multiple failures or different combinations of failure) relate to PCM impairment. Aim 3 will use biomechanical analysis of muscle and connective tissue interactions in computer-based models of CTS and PCM to investigate patterns of muscle and connective support site failures that lead to AVP. These insights are needed to advance disease mechanisms research in order to reduce the 30% recurrence rate with surgery, and develop preventative strategies to lessen the need for surgery in 400,000 women a year.